Z Geburtshilfe Neonatol 2011; 215 - FV12_02
DOI: 10.1055/s-0031-1293277

Genetic Low Nephron Number Hypertension is Associated with Altered Expression of Osteopontin and One of Its Receptors, CD44, but not Alpha(v)-Integrin during Nephrogenesis

AL Freese 1, M Wehland 2, F Freese 3, A Schulz 4, R Kreutz 5, L Rothermund 6
  • 1Klinik für Geburtsmedizin, Charité - Universitätsmedizin Berlin, Berlin
  • 2Institut für Klinische Pharmakologie und Toxikologie, Campus Benjamin Franklin und Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin
  • 3Klinik für Mund-, Kiefer und Gesichtschirurgie, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin
  • 4Institut für Klinische Pharmakologie und Toxikologie, Campus Benjamin Franklin und Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin
  • 5Institut für Klinische Pharmakologie und Toxikologie, Campus Benjamin Franklin und Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin
  • 6Institut für Klinische Pharmakologie und Toxikologie, Campus Benjamin Franklin und Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin

Ziel: Low nephron number may represent a major determinant of human primary hypertension in adult life. This hypothesis is supported by a genetic rat model, the Munich-Wistar Frömter (MWF) rat, which demonstrates an inherited deficit in nephron number and the development of spontaneous hypertension.

Osteopontin and its receptors cd44 and alpha(v)beta(3)integrin play a role in growth and differentiation processes during nephrogenesis. We demonstrate that the low nephron number present during fetal development is associated with altered expression of osteopontin and one of its receptors, cd44, but not alpha(v)-integrin in MWF.

Methodik: We compared MWF and normal Wistar rats during nephrogenesis at day 19 of fetal development (E19) and adult rats at postnatal day 7 (D7). Quantitative mRNA expression was determined by RT-PCR. Protein expression was measured by ELISA.

Ergebnis: At E19 in MWF renal mRNA-expression and protein-expression of OPN was decreased (–75%, P < 0,05; –44%,P < 0,05). mRNA-expression of cd44 was increased (+270%, P < 0,05).

At D7 in MWF renal mRNA-expression of OPN was back to control but renal protein-expression was increased (+107%, P < 0,05). Renal mRNA-expression of cd44 remained elevated (+127%, P < 0,05).

Schlussfolgerung: The altered fetal expression of the Osteopontin-cd44-integrin-receptor-system molecules in the MWF model may indicate a link to fetal development of low nephron number with manifestation of genetic hypertension in adult life.

Literatur: L. Rothermund, et al., "Genetic low nephron number hypertension is associated with dysregulation of the hepatic and renal insulin-like growth facor system during nephrogenesis," J. Hypertens. 24(9), 1857 (2006).

Integrin alpha(v). - Osteopontin - cd44 - fetal programming - hypertension - kidney development - low nephron number